AUTHOR=Chen Zhichu , Huang Dong , Yongyut Prakaiwan , Li Guangbin , Esteban María Ángeles , Jintasataporn Orapint , Deng Junming , Zhang Wenbing , Ai Qinghui , Mai Kangsen , Zhang Yanjiao 

TITLE=Vitamin D3 deficiency induced intestinal inflammatory response of turbot through nuclear factor-κB/inflammasome pathway, accompanied by the mutually exclusive apoptosis and autophagy

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.986593

DOI=10.3389/fimmu.2022.986593

ISSN=1664-3224

ABSTRACT=<p>Vitamin D<sub>3</sub> (VD<sub>3</sub>) participated widely in the nuclear factor-κB (NF-κB)-mediated inflammation, apoptosis, and autophagy through the vitamin D receptor (VDR). However, the molecular mechanisms remain not understood in teleost. The present study investigated the functions of VD<sub>3</sub>/VDR on intestinal inflammation, autophagy, and apoptosis of turbot <italic>in vivo</italic> and <italic>in vitro</italic>. Triple replicates of 30 fish were fed with each of three diets with graded levels of 32.0 (D<sub>0</sub>), 1012.6 (D<sub>1</sub>), and 3978.2 (D<sub>2</sub>) IU/kg VD<sub>3</sub>. Obvious intestinal enteritis was observed in the D<sub>0</sub> group and followed with dysfunction of intestinal mucosal barriers. The intestinal inflammatory response induced by VD<sub>3</sub> deficiency was regulated by the NF-κB/inflammasome signalling. The promotion of intestinal apoptosis and suppression of intestinal autophagy were also observed in the D<sub>0</sub> group. Similarly, VD<sub>3</sub> deficiency <italic>in vitro</italic> induced more intense inflammation regulated by NF-κB/inflammasome signalling. The mutually exclusive apoptosis and autophagy were also observed in the group without 1,25(OH)<sub>2</sub>D<sub>3</sub><italic>in vitro</italic>, accompanied by similar changes in apoptosis and autophagy increased apoptosis. The gene expression of VDRs was significantly increased with the increasing VD<sub>3</sub> supplementation both <italic>in vivo</italic> and <italic>in vitro</italic>. Moreover, VDR knockdown in turbot resulted in intestinal inflammation, and this process relied on the activation of inflammasome mediated by NF-κB signalling. Simultaneously, intestinal apoptosis was promoted, whereas intestinal autophagy was inhibited. In conclusion, VD<sub>3</sub> deficiency could induce intestinal inflammation <italic>via</italic> activation of the NF-κB/inflammasome pathway, intestinal apoptosis, and autophagy formed a mutually exclusive relation in teleost. And VDR is the critical molecule in those processes.</p>